PROJECT SUMMARY Studies of model organisms have revealed many insights into how animals sense their environment and how this input is processed by their brains to produce behavioral output. However, our current understanding of how the brain controls behavior is derived from a handful of species that share certain features, e.g., their brains are highly regionalized and stereotyped. Yet, not all animal brains are structured in this manner, and to identify general principles for the control of animal behavior, a broader diversity of brains needs to be investigated. We will study the acoel worm, Hofstenia miamia, which is a new research organism with key features that position it to address major questions in behavioral neuroscience. First, Hofstenia, a voracious mangrove predator, is a marine invertebrate that performs complex behaviors in the lab, and our recent work has shown that it is amenable to rigorous, quantitative studies of its behaviors and of behavior-induced physical changes in its aquatic environment. Second, as an acoel, Hofstenia diverged from models such as flies and mice 550 million years ago and possesses a brain that does not show evidence of regionalization, providing an opportunity to study distributed computation. Third, the Hofstenia brain can regenerate from any starting condition, enabling the study of how robustness is encoded in the brain. Fourth, Hofstenia is highly tractable in the lab, offering many genomic resources and tools for functional genetics, which will make it possible to collect neural activity data. Given these features, the overall objective in this proposal is to leverage Hofstenia to study its behavior and environment at the whole-organism level. Specifically, we aim to: 1) Develop methods for rigorous measurement and quantification of worm behavior and its environment, using pose estimation to infer worm action sequences, water flow measurement to quantify physical changes around worms, and tracking of prey to quantify the worm’s biological environment. 2) Perturb both organism and environment to uncover mechanisms of behavioral control. We will amputate animals to determine how regenerating brain features correlate with elements of behavior, and deliver artificial mechanical flow stimuli to understand how animals read their physical environment. 3) We will assemble a team of researchers with expertise in behavioral neuroscience, pose estimation, connectomics, neural activity dynamics, fluid mechanics, computational modeling of behavior, and in the organism and its regenerative abilities to plan work that will enable the integration of neural activity data with behavioral and environmental data to reveal how distributed computations in the brain enable the animal to produce action sequences that successfully navigate the environment and capture prey. This proposal is innovative in its use of a new research organism, in its pursuit of behavior-environment quantification in the whole-organism context, and in its potential to reveal general principles of behavioral control, particularly via distributed computation.

PROJECT NARRATIVE This project aims to develop a new animal model for neuroscience that allows synchronous measurement of behavior and of the environment at the level of the whole organism. This species possesses the remarkable capacity to maintain robust brain function despite substantial damage and is also amenable to measurement of neural activity. In the long term, this work will reveal fundamental principles of how the brain controls behavior and its robustness.